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  Kindlin-3-mediated integrin adhesion is dispensable for quiescent but essential for activated hematopoietic stem cells

Ruppert, R., Moser, M., Sperandio, M., Rognoni, E., Orban, M., Liu, W.-H., et al. (2015). Kindlin-3-mediated integrin adhesion is dispensable for quiescent but essential for activated hematopoietic stem cells. JOURNAL OF EXPERIMENTAL MEDICINE, 212(9), 1415-1432. doi:10.1084/jem.20150269.

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 Creators:
Ruppert, Raphael1, Author              
Moser, Markus1, Author              
Sperandio, Markus2, Author
Rognoni, Emanuel1, Author              
Orban, Martin2, Author
Liu, Wen-Hsin1, Author              
Schulz, Ansgar S.2, Author
Oostendorp, Robert A. J.2, Author
Massberg, Steffen2, Author
Fässler, Reinhard1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Free keywords: BONE-MARROW MICROVESSELS; LEUKOCYTE ADHESION; PERIPHERAL-TISSUES; ENDOTHELIAL-CELLS; MEDIATES ADHESION; PROGENITOR CELLS; FETAL LIVER; IN-VIVO; NICHE; BETA-1-INTEGRIN
 Abstract: Hematopoietic stem cells (HSCs) generate highly dividing hematopoietic progenitor cells (HPCs), which produce all blood cell lineages. HSCs are usually quiescent, retained by integrins in specific niches, and become activated when the pools of HPCs decrease. We report that Kindlin-3-mediated integrin activation controls homing of HSCs to the bone marrow (BM) and the retention of activated HSCs and HPCs but not of quiescent HSCs in their BM niches. Consequently, Kindlin-3-deficient HSCs enter quiescence and remain in the BM when cotransplanted with wild-type hematopoietic stem and progenitor cells (HSPCs), whereas they are hyperactivated and lost in the circulation when wild-type HSPCs are absent, leading to their exhaustion and reduced survival of recipients. The accumulation of HSPCs in the circulation of leukocyte adhesion deficiency type III patients, who lack Kindlin-3, underlines the conserved functions of Kindlin-3 in man and the importance of our findings for human disease.

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Language(s): eng - English
 Dates: 2015
 Publication Status: Published in print
 Pages: 18
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000360379800011
DOI: 10.1084/jem.20150269
 Degree: -

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Title: JOURNAL OF EXPERIMENTAL MEDICINE
Source Genre: Journal
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Publ. Info: 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA : ROCKEFELLER UNIV PRESS
Pages: - Volume / Issue: 212 (9) Sequence Number: - Start / End Page: 1415 - 1432 Identifier: ISSN: 0022-1007